Herpesviruses

Important Characteristics

Virion: Spheric (Icosahedral), d = 150 200 nm

Genom: dsDNA, linear, 123 235 kbp, repeated sequences

Proteins: > 35 proteins inside virion, synthesized in host

nucleus

Envelope: Contain viral glycoproteins, Fc receptor,

originated from nuclear membrane

Replication: Nucleus, budding from nuclear membrane

Etc:
Codes many enzymes
Causes latent infections, some causes cancer
Reactivated by immunosuppression

Famili

Herpesvirid
ae

Virio
n

Genom
e
replic.

Nucleocap
sid form.

Virion
Maturati
on
M

MC
(hrs)
15-72

Classifications

Divided into 3 Subfamilies:

Alpha ()

Beta ()

HHV-1
HHV-2
HHV-3
HHV-5
HHV-6
HHV-7

Gamma ()

HHV-4
HHV-8

Aplhaherpesvirinae

Alphaherpesvirinae

Consists of

HHV-1 Herpes Simplex Virus type 1

HHV-2 Herpes Simplex Virus type 2
HHV-3 Varicella-Zoster Virus

Known for its relatively short reproductive

cycle, targeting mainly epithelial cells, and
causing latent infections in neurons

The most important herpesviruses in animal

virology

Herpes Simplex Virus type 1 / HSV-1

Cause

Gingivostomatitis
Pharyngotonsilitis
Herpes labialis
Keratoconjunctivitis
Encephalitis (10-20%)
Genital herpes
(uncommon)

Transmitted through
direct contact or oral
secretions

Glycoproteins

gC complement
binding protein (C3b)
gD enable entry to
host cell
gE Fc receptor, binds
to IgG Fc and
inactivates neutralizing
agents
gG discriminate HSV1 (gG-1) to HSV-2 (gG1)

Latent in trigeminal ganglia (tendency,

not absolute)

Herpes Simplex Virus type 2/ HSV -2

Cause

Meningitis
Genital herpes
Neonatal herpes
congenital, mortality
65%
Oral herpes
uncommon

Transmitted through
sexual contact and
perinatally (prev:
cesarean)

Same glycoproteins as HSV-1

Latent usually in sacral root ganglia

HSV-1 and HSV-2 Replication

Infect cell, produce early, immediate-early, and late proteins

Early proteins used in regulation of genetic replication of the
virus.
-TIF protein joins the viral particle and aids in immediateearlytranscription. Tegument shutoff protein (VHS or UL41) is
very important to viral replication. This enzyme shuts off
protein synthesis in the host, degrades hostmRNA, helps in
viral replication, and regulatesgene expressionof viral proteins.
The late proteins are used to form the capsid and the receptors
on the surface of the virus. Packaging of the viral particles
including the genome core and thecapsid- occurs in the
nucleus of the cell. HSV-1 undergoes a process of primary and
secondary envelopment. The primary envelope is acquired by
budding into the inner nuclear membrane of the cell. This then
fuses with the outer nuclear membrane releasing a naked
capsid into the cytoplasm. The virus acquires its final envelope
by budding into cytoplasmicvesicles.

Varicella-Zoster Virus / VZV

Cause

Varicella (Chickenpox)
Zoster (Shingles)

Chickenpox
asynchronous vesicle,
occurs primarily on trunks,
lesions are superficial,
contagious before
symptomps appear
Zoster reactivation of
VZV, increased occurance
with age and impaired
immune function

Presentation in Immunocompromised
patients

Zoster multiplex
Zoster sine herpete
Myelitis
Keratitis

Latent usually in dorsal root ganglia

Lab Diagnosis

Cytopathology

Virus isolation and identification

Immunofluorescent test distinguish HSV-1 to

HSV-2

PCR

Rapid Giemsa stain (Tzank smear), shows

multinulcleated giant cells
Cannot differentiate between HSV-1, HSV-2, and
VZV

Use CSF for HSV in CNS

Serology

Use of specific-type HSV antibody

Betaherpesvirinae

Betaherpesvirinae

Consists of

HHV-5 Cytomegalovirus (CMV)

HHV-6 Roseolavirus
HHV-7 Pityriasis Rosea

Known for its long reproductive cycle, often

causing infected cells to become enlarged,
and become latent in a variety of tissues

HHV-6 is divided into HHV-6A and HHV-6B, and

classified as distinct species in 2012

Cytomegalovirus / CMV

Cause
Heterophile-negative
mononucleosis
syndrome
Cytomegalic
inclusion disease
IC patients:
pneumonia,
hepatitis,
encephalitis,
retinitis, neuropathy)

Cytomegalic inclusion disease:

Bone pain
Nausea and vomitting
Jaundice
Splenomegaly
Thrombocytopenia
Mental retardation
Microcephaly
Calcifications of CNS
and kidney

Congenital CMV infection Most common

cause of congenital abnormalities, most at
risk of infection during the 1st trimester

HIV patients CMV retinitis (20 30%)

Lab Diagnosis

Virus isolation

PCR
Antigen Detection Test

Translucent cells, enlarged with giant intranuclear

inclusion Owls eye
Slow, needs 2 3 weeks

Monoclonal antibody against viral antigen

Serology

IgM for new infection, IgG for past infection

Owls eye inclusion bodies

HHV-6

Disease: Roseola infantum /

Exanthema Subitum / The Sixth
Disease (HHV-6B)

Abrupt onset of high fever for 3

5 days followed by erythematous
maculopapular rash that appears
with the return of normal
temperature

HHV-6A : more neurovirulent,

usually found in patients with
multiple sclerosis

Cellular receptor : CD46

Transmission: via saliva of

parents, 90% seropositivity in
older than 2 years children

Treatment: Symptomatic, use of

Ganciclovir have shown some success

Gammaherpesvirinae

Gammaherpesvirinae

Consists of

HHV-4 Epstein-Barr Virus (EBV)

HHV-8 Kaposis Sarcoma-associated Herpesvirus (KSHV)

Known for its variable reproductive cycle time,

infects and become latent in primarily
lymphoid tissue

Epstein-Barr Virus / EBV

Cause
Infectious Mononucleosis
Associated with Ca
nasopharyngeal and
Burkitts lymphoma
IC patients: hairy cell
leukoplakia
Primarily infect and become
latent in B-cells

EBVs infectious mononucleosis is

heterophile positive; it generates IgM
and agglutinate sheep and horse RBC

No antiviral drugs or vaccines available

Infects B cell by binding to

complement component C3d
receptor becomes latent in
B cell and immortalizes B cell
virus persistence, limited
viral expression, potential to
reactivate and lytic replicate
Antigen
Latent: EBNA (gene
regulation,extrachromosom
al replication), EBER
(untranslated RNA and LMP
(growth)

Early: nonstructural
proteins, marks the start
of replication
Late: structural
components of viral
capsid and glycoproteins

Replications:
Lytic replication, can occur
both in B cell (needs
reactivation) or epithelial
cell (right after entry)
Marked by production of
early antigen proteins

Lab Diagnosis

Virus Isolation and Identification

Nucleic Acid Hybridisation identifies EBER from

infected cells
Immortalized B cell culture

Serology

ELISA
Immunoblot assay
Immunofluorescent test
Heterophile agglutination test

HHV-8

Associated with Kaposis

Sarcoma

KS: vascular neoplasm that

manifests in the skin and
other organs. Usually begins
as a red/purple patch that
becomes nodular and plaquelike. Most common
malignancy in AIDS patients
Presents at death, but not
necessarily causes it

Transmitted mainly through man-to-man

sexual activities and through organ
transplantation

Lab Diagnosis:

HHV-8 innactivates tumor

suppressor gene
retinoblastoma protein
indirectly causing KS

Biopsy
PCR
ELISA
Immunoblot assay
Indirect
Immunofluorescent
HHV-8 DNA/RNA detection

Treatment: Ganciclovir, Cidofovir, Foscarnet,

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